Piotr Cysewski

A post-SCF complete basis set study on the recognition patterns of uracil and cytosine by aromatic and π–aromatic stacking interactions with amino acid residues

The DF-MP2 quantum chemistry method was applied to a description of the stacking interactions of uracil and cytosine with five model amino acid residues, namely histidine (HIS), phenylalanine (PHE), tyrosine (TYR), tryptophan (TRP) and an arginyl moiety (ARG). The BSSE and complete basis set corrections were taken into account. Both uracil (U) and cytosine (C) may strongly interact with amino acid residues. The stacking energy is very sensitive to both the nature of the interacting monomers and their spatial conformations. However, usually considerable configurational degrees of freedom are observed, leading to similar stacking energies. The overall order of optimized stacking complexes corresponds to the following sequence: C-TRP (-16.0 kcal mol(-1)) > U-TRP (-13.5 kcal mol(-1)) > U-TYR (-12.2 kcal mol(-1)) > U-HIS (-8.7 kcal mol(-1)) > U-PHE (-7.7 kcal mol(-1)) > C-PHE (-6.6 kcal mol(-1)). Cytosine may also strongly attract HIS and TYR via stacking interactions but the corresponding minima were not found since hydrogen-bonded pairs are result of gradient optimizations. Besides, stacking imposes an increase in aromatic character on both analyzed pyrimidines. This is consistently described by changes of both energetic and structural aromaticty indices. There are also observed changes in aromaticities of amino acid residues but the predictions by the harmonic oscillator model of aromaticity (HOMA) index and nucleus-independent chemical shifts (NICS) are inconsistent. Finally, there is also an interesting observation with respect to the extrapolation of the stacking energies: the same quality of complete basis set limits may be obtained without actual calculations on the aug-cc-pVQZ basis set and application of the extrapolation procedure twice gives substantially the same complete basis set results within 0.1 kcal mol(-1).

Environment influences on the aromatic character of nucleobases and amino acids

Geometric (HOMA) and magnetic (NICS) indices of aromaticity were estimated for aromatic rings of amino acids and nucleobases. Cartesian coordinates were taken directly either from PDB files deposited in public databases at the finest resolution available (≤1.5u2009Å), or from structures resulting from full gradient geometry optimization in a hybrid QM/MM approach. Significant environmental effects imposing alterations of HOMA values were noted for all aromatic rings analysed. Furthermore, even extra fine resolution (≤1.0u2009Å) is not sufficient for direct estimation of HOMA values based on Cartesian coordinates provided by PDB files. The values of mean bond errors seem to be much higher than the 0.05u2009Å often reported for PDB files. The use of quantum chemistry geometry optimization is strongly advised; even a simple QM/MM model comprising only the aromatic substructure within the QM region and the rest of biomolecule treated classically within the MM framework proved to be a promising means of describing aromaticity inside native environments. According to the results presented, three consequences of the interaction with the environment can be observed that induce changes in structural and magnetic indices of aromaticity. First, broad ranges of HOMA or NICS values are usually obtained for different conformations of nearest neighborhood. Next, these values and their means can differ significantly from those characterising isolated monomers. The most significant increase in aromaticities is expected for the six-membered rings of guanine, thymine and cytosine. The same trend was also noticed for all amino acids inside proteins but this effect was much smaller, reaching the highest value for the five-membered ring of tryptophan. Explicit water solutions impose similar changes on HOMA and NICS distributions. Thus, environment effects of protein, DNA and even explicit water molecules are non-negligible sources of aromaticity changes appearing in the rings of nucleobases and aromatic amino acids residues.

Linear and nonlinear optical properties of azobenzene derivatives

The results of computations of spectroscopic parameters of lowest–lying electronic excited states of azobenezene derivatives are presented. The analysis of experimentally recorded spectra was supported by quantum chemical calculations using density functional theory. The theoretically determined resonant (two-photon absorption probabilities) and non-resonant (first-order hyperpolarisability) nonlinear optical properties are also discussed, with an eye towards the performance of recently proposed long-range corrected (LRC) schemes (LC–BLYP and CAM–B3LYP functionals).

Effect of 2'-deoxyguanosine oxidation at C8 position on N-glycosidic bond stability.

Abstract 8-Oxo-2′-deoxyguanosine, 8-Oxoguanine, 8 -Hydroxyguanine, Base Modification, DNA Oxidative Damage The influence of 2′-deoxyguanosine (dG) oxidation at the C-8 position on N-glycosidic bond stability was in vestigated. A kinetic analysis of dG and 8-oxo-2′-deoxy-guanosine (8-oxodG) depurination reactions was carried out in water solutions at pH ranging from 2 to 7.4 and temperature of 100 °C. The results indicate that N-glyco sidic bond of 8-oxodG is significantly more stable in comparison with dG at any pH applied. At pH 5.1 hydrolysis rate of dG is 4.5-fold higher than that for 8-oxodG. The chemical stability of the modified nucleo side in oxidatively damaged DNA is one of important factors contributing to its mutagenic potential. Results of our experiments indicate that 8-oxodG, potentially mutagenic and carcinogenic nucleoside, is hardly suscep tible to spontaneous depurination and its removal from cellular DNA depends mostly on the activity of DNA repair enzymes.

Spectroscopic and nonlinear optical properties of new chalcone fluorescent probes for bioimaging applications: a theoretical and experimental study

AbstractIn this study, the newly synthesized non-centrosymmetric, 4-dimethylamino-3′-isothiocyanatochalcone (PKA) compound was presented. This compound belongs to the chalcone group, and its main purpose is to be used in biomedical imaging as a fluorescence dye. For this reason, the linear and nonlinear properties in solvents of different polarity were thoroughly studied. In accordance with the requirements for a fluorochrome, the PKA compound is characterized by strong absorption, large Stokes’ shifts, relatively high fluorescence quantum yields and high nonlinear optical response. Moreover, the isothiocyanate reactive probe was conjugated with Concanavalin A. Conventional fluorescence microscopy imaging of Candida albicans cells incubated with the PKA-Concanavalin A, is presented. The results of this study show that the novel conjugate PKA-Concanavalin A could be a promising new probe for cellular labelling in biological and biomedical research.n Graphical abstractSpectroscopic behavior of the PKA dye

Color prediction from first principle quantum chemistry computations: a case of alizarin dissolved in methanol

The electronic spectrum of alizarin (AZ) in methanol solution was measured and used as reference data for color prediction. The visible part of the spectrum was modelled by different DFT functionals within the TD-DFT framework. The results of a broad range of functionals applied for theoretical spectrum prediction were compared against experimental data by a direct color comparison. The tristimulus model of color expressed in terms of CIE XYZ and CIE Lab parameters was applied both to experimental and predicted spectra. It was found that the HSE03 method along with the 6-31G(d,p) basis set provides the most accurate color prediction, much better than other commonly used functionals such as B3LYP, CAM-B3LYP or PBE0. Besides, the influence of potential errors, introduced by theoretical predictions on color estimation, was examined for different wavelengths. The obtained results showed that color prediction is significantly dependent on the type of basis set and functional applied. The proposed methodology provides a simple, straightforward and more reliable way of theoretical protocols validation than just a comparison of experimental and estimated values of maximum absorbance wavelength.

An ab initio SCF study on the tautomerisation of the 8-oxo-guanine and xanthine

Abstract All possible H 9 -tautomers of 8-oxo-guanine and xanthine were studied by means of PM3 semiempirical and DFT (density functional theory) quantum chemistry methods. Additionally, the five most stable tautomers of both guanine derivatives were estimated on 3-21G, 6-31G, 6-31G ∗∗ and MP2 (6-31G ∗∗ ) ab initio levels. The impact of the environment polarity on the tautomeric equilibrium was also taken into account. Among the variety of tautomeric isomers most probable are diketo forms of both studied derivatives in non-polar and polar surroundings. The tautomeric equilibrium was unchanged after connection of the sugar backbone. The most preferred diketo forms of 8-oxo-guanosine and xanthidine are in syn conformations both in polar and non-polar environments. The increase of the syn conformations over anti ones may have the source in the formation of the internal hydrogen bonds between H′5 and N 3 , atoms. The calculated values of the pseudorotation phase angle were between 144 and 180° in all cases. This corresponds to C′2-endo conformations of all optimised structures. The N-glycosidic bond stability of most stable tautomers was compared to standard guanosine. Most tautomers of 8-oxoguanosine and xanthidine are characterised by more stable C 1 ′ue5f8N 9 bond. This indicates that both these derivatives are hardly susceptible to spontaneous depurination and its removal from the DNA will depend mostly on the activity of DNA repair enzymes.

Heat of formation distributions of components involved in bi-component cocrystals and simple binary eutectic mixtures

A computationally inexpensive screening tool was formulated allowing for rational pre-selection of components as the most promising candidates for synthesis of two-component cocrystals. The proposed procedure relies on the scoring function quantifying dissimilarity of 2D histograms, which describe distributions of heat of formation resulting from two counterparts of database consisting of 1599 cocrystals and 492 cases of pairs immiscible in the solid state. It has been observed that higher probability of cocrystal formation is to be expected if components differ by heat of formation (Hf) values and at least one of components is hydrophilic. This observation was also validated based on an additional 1590 cocrystals not included in the training set. On the contrary, the high probability of simple eutectic systems is expected for cases of high similarities and positive values of Hf. Based on the formulated scoring function, the regions of observed highest probability of cocrystallization can be identified. Although the proposed phenomenological approach cannot provide absolute prediction of cocrystal formation, it does offers practical and simple guidance for rationalizing the selection of potential components for real practical purposes.

Intra-strand stacking interactions in B-DNA crystals characterized by post-SCF quantum chemistry computations

The distributions of intermolecular interaction energies (IIE) of all possible 5′-X/Y-3′ (X, Y = A, G, T, C) stacked pairs in conformations exactly matching to intra-strand orientations occurring in crystallographic B-DNA double strands were characterized by quantum chemistry calculations on MP2/aug-cc-pvDZ level. The essential feature of this approach is sampling over meaningful conformations and getting statistically significant data on the energetics of stacking interactions in B-DNA crystals. Based on the most frequently occurring IIE values (in kcal mol−1) the following order of the intra-strand stacking interactions in B-DNA solids is concluded: G/A −10.2 ± 1.1 > A/G −9.2 ± 1.0 ≈ G/C −8.7 ± 1.2 > A/A −8.3 ± 1.0 > A/T −7.7 ± 0.9 > C/G −7.2 ± 0.9 > T/G −6.5 ± 1.3 ≈ A/C −6.2 ± 0.8 ≈ G/T −6.2 ± 1.3 > T/A −5.6 ± 0.9 > G/G −5.1 ± 1.1 > T/C −4.9 ± 0.7 > C/T −4.8 ± 1.1 > T/T −4.7 ± 0.5 > C/A −3.8 ± 0.8 > C/C −1.0 ± 1.0 (standard deviations are provided in parenthesis). Sequence-related structural diversities and SCF and correlation contributions to the stacking interactions are also discussed. The most representative structures of stacked dimers were found based on a clustering protocol.

Structure and tautomeric properties of thymine derivatives generated by hydroxyl radical in aerobic conditions

The tautomeric properties of five hydroxyl radical-induced thymine derivatives: thymine glycol (1), 5-formyldeoxyuracil (2), 5-hydroxymethyluracil (3), N-tatronyluridine (4) and 5-hydroxymethylhydantoine (5) were characterised by abinitio HF (6-311G**), MP2 (6-311G**) and SCI-PCM (6-311G**) quantum chemistry calculations. Amongst all the tautomers of 1 the I-5eq6ax tautomer (the diketo form with C5 equatorial and C6 axial orientations of the hydroxy groups) is the most stable, in both polar and non-polar environments. The most stable tautomer of 2 is the diketo form with the carbonyl group oriented in such a way that the maximum distance between O4 and OC5 oxygen atoms is preserved. By analogy, the preferred tautomeric form of 3 corresponds to the diketo isomer. Among the potential 43 isomers of 4 the most stable is that in the diketo-amino form with anti-conformation of the C2–N3–C4–C5 torsion angle and equatorial conformation of the C5 chirality centre. Finally, the most probable structure of 5 is the diketo tautomeric form.